Polyamidoamine Dendrimers Can Improve the Pulmonary Absorption of Insulin and Calcitonin in Rats

Dong, Zihui; Hamid, Khuriah Abdul; Gao, Yang; Yang, Lin; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

doi:10.1002/jps.22428

Cited by 64 publications

(43 citation statements)

References 55 publications

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“…One should keep in mind that this pH based vectorization may impose administration restrictions as for example in the case of oral administration due to the low pH of the stomach. Nevertheless, recent studies have shown that PAMAM dendrimers have potential for pulmonary inhalation, [103,104] which may be highly advantageous in the case of tuberculosis treatment. …”

Section: Tionsmentioning

confidence: 99%

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Bellini

Guimarães

Pacheco

et al. 2015

Journal of Molecular Graphics and Modelling

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The association of the anti-tuberculosis drug rifampicin (RIF) with a 4th-generation poly(amidoamine) (G4-PAMAM) dendrimer was investigated by means of molecular dynamics simulations. The RIF load capacity was estimated to be around 20 RIF per G4-PAMAM at neutral pH. The complex formed by 20 RIF molecules and the dendrimer (RIF20-PAMAM) was subjected to 100 ns molecular dynamics (MD) simulations at two different pH conditions (neutral and acidic). The complex was found to be significantly more stable in the simulation at neutral pH compared to the simulation at low pH in which the RIF molecules were rapidly and almost simultaneously expelled to the solvent bulk. The high stability of the RIF-PAMAM complex under physiological pH and the rapid release of RIF molecules under acidic medium provide an interesting switch for drug targeting since the Mycobacterium resides within acidic domains of the macrophage. Altogether, these results suggest that, at least in terms of stability and pH-dependent release, PAMAM-like dendrimers may be considered suitable drug delivery systems for RIF and derivatives.

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Section: Tionsmentioning

confidence: 99%

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Bellini

Guimarães

Pacheco

et al. 2015

Journal of Molecular Graphics and Modelling

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“…The pulmonary absorption of calcitonin and insulin were estimated by measuring the plasma calcium and glucose levels, respectively, as reported previously (He et al, 2007;Dong et al, 2011). Plasma calcium concentration was measured by Calcium Test Kit and plasma glucose level was measured using Glucose Test Kit with the glucose oxidase method.…”

Section: Methodsmentioning

confidence: 99%

Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats

Zhang

Huang

Sun

et al. 2015

International Journal of Pharmaceutics

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“…The potential biomedical application of inhaled dendrimers was first realised almost 2 decades ago by Baker and colleagues who examine the ability to delivery DNA to the lungs using a PAMAM dendrimer carrier and to use sialic acid conjugated dendrimers to treat influenza pneumonitis [42,43]. Following on from these earlier studies, subsequent studies aimed to use PAMAM dendrimers as carriers for methylprednisolone (to treat lung inflammation) [44], peptide phage clones to enhance dendrimer absorption from the lungs [45] and to improve the systemic absorption of peptides and proteins, such as heparin [46,47], calcitonin and insulin [48]. To this point however, only PAMAM dendrimers had been used, and none of the studies had systematically characterised the effect of dendrimer size or charge on pulmonary pharmacokinetics…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Polymer-drug conjugates as inhalable drug delivery systems: A review

Marasini

Haque

Kaminskas

2017

Current Opinion in Colloid & Interface Science

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Abstract:Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetics profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety with the lungs, which is closely linked to their retention time in the lungs. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments on several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps. Graphical abstract:

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Polyamidoamine Dendrimers Can Improve the Pulmonary Absorption of Insulin and Calcitonin in Rats

Cited by 64 publications

References 55 publications

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Improvement of pulmonary absorption of poorly absorbable macromolecules by hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) in rats

Polymer-drug conjugates as inhalable drug delivery systems: A review

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